Psilocybin Efficacy and Mechanisms of Action in Major Depressive Disorder: a Review.
Damien Prouzeau, Ismaël Conejero, Peter L Voyvodic, Carine Bécamel, Mocrane Abbar, Jorge Lopez-Castroman
Current Psychiatry Reports October 1, 2022 DOI: 10.1007/s11920-022-01361-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Intervention | Psilocybin |
| Topics | Depression Psilocybin |
| Keywords | 5-ht2a agonists Hallucinogen Mood disorder Narrative review Neuroimaging Psychedelic |
| Citations | 32 |
| Key findings | Psilocybin has large, rapid, and persistent clinical effects in treating resistant or end-of-life depression, but one trial against escitalopram did not show significant superiority on the main outcome. |
Abstract
We aim to provide an overview of the current state of knowledge about the efficacy of psilocybin in the treatment of depression, as well as its mechanisms of action. Psilocybin has a large, rapid, and persistent clinical effect in the treatment of resistant or end-of-life depression. Tolerance is good, with mild side effects limited to a few hours after dosing. The studies conducted to date have had small sample sizes. One clinical trial has been conducted against a reference treatment (escitalopram) without showing a significant superiority of psilocybin in the main outcome. The neurobiological mechanisms, mostly unknown, differ from those of SSRI antidepressants. Psilocybin represents a promising alternative in the treatment of depression. Further research with larger sample sizes, particularly against reference treatments, is needed to better understand the neurobiological factors of its effects and to investigate its potential for use in everyday practice.
Comparable studies
Other narrative reviews on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression | 2021 | Review | |
| Registered clinical studies investigating psychedelic drugs for psychiatric disorders. Registered clinical trials on clinicaltrials.gov evaluating psychedelics for... | 2021 | Review | n = 70 |
| Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. A Review | 2020 | Review | |
| From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders | 2021 | Review |
Citations in the library
Cited by 24
- Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. Neuropsychopharmacology September 1, 2023
- Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis BMJ May 1, 2024
- Antidepressant-like effects of psychedelics in a chronic despair mouse model: is the 5-HT2A receptor the unique player? Neuropsychopharmacology March 1, 2024
- Rapid antidepressant-like effect of non-hallucinogenic psychedelic analog lisuride, but not hallucinogenic psychedelic DOI, in lipopolysaccharide-treated mice Pharmacology, Biochemistry, and Behavior December 5, 2022
- The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression. Journal of Affective Disorders March 1, 2025
and 19 more in the library
Cites 46
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
and 41 more in the library